Current Drug Delivery - Volume 17, Issue 9, 2020

The conventional treatment regimen for cancer with a single chemotherapeutic agent is far behind the clinical expectations due to the complexity of cancer biology and is also associated with poor Quality of Life (QOL) due to off-site toxicity and multidrug resistance. In recent years, nanopotentiated combination therapy has shown significant improvement in cancer treatment via a synergistic approach. However, being synthetic in nature, nanocarriers have been associated with the activation of the Complement (C) activation system resulting in serious hypersensitivity reactions known as CActivation Related Pseudoallergy (CARPA) effect once given via intravenous injection. On the other hand, nanopotentiated oral drug delivery offers several advantages for the effective and safe delivery of the drug to the target site. This hypothesis aims to put forward wherein Exemestane (chemotherapeutic agent) and lycopene (herbal bioactive) co-laden into PEGylated liposomes and delivered to the breast cancer via the oral route. PEGylation of the liposomes would prevent both molecules from the harsh microenvironment of the Gastrointestinal Tract (GIT) and would eventually promote their intestinal absorption via the lymphatic pathway to the systemic circulation. Lycopene being a potent antioxidant and anti-cancer herbal bioactive would promote the therapeutic efficacy of the Exemestane via a synergistic approach. This nanopotentiated oral combination therapy would pave the path for the safe and effective treatment of cancer.

Nowadays, the focus has been shifted to new technologies for improving drug solubility, permeability, and bioavailability, amid unprecedentedly increasing the number of newly discovered Active Pharmaceutical Ingredients (APIs), which are mostly categorized under Biopharmaceutical Classification System (BCS) as class-II and class IV. Traditional technologies and classical formulation strategies often fail to address most of the formulation problems associated with new APIs, particularly solubility and bioavailability. Therefore, exploring new and innovative technologies on an industrial scale is a prerequisite and requires modernization of manufacturing processes, as well as more advanced research and development. Liquisolid technology is a new, innovative industrial technology, particularly designed for either improving the release rates of poorly absorbed drugs or controlling their release pattern by achieving sustained-release profiles with zero-order release kinetics. Besides, it is a promising photoprotective system for photosensitive drugs and can further be used for modulating the drug microenvironmental pH. The next generation of liquisolid systems stems from a set of emerging technologies, such as liqui-pellet technology, which originates from combining liquisolid technology with pelletization technique, particularly extrusion-spheronization technique. This review article highlights the current state of liquisolid technology, ongoing challenges, characterization and applications, possible future prospects, the advent of new and emerging technologies, and the revolution of the next generation of liquisolid technology.

Alginates are biopolymers usually obtained from brown seaweed, brown algae (Ochrophyta, Phaeophyceae), and bacteria (Azatobacter vineland and Pseudomonas species) belonging to the family of polycationic copolymers. They are biocompatible, biodegradable, non-antigenic, and non-toxic biopolymer with molecular mass ranges from 32,000-40,000 g/mol in commercial grades. These can be used as edible films or coatings in food industries and also some natural or chemical additives could be incorporated into them to modify their functional, mechanical, nutritional as well as organoleptic properties. Due to their high viscosity and extraordinary shear-thinning effect, they can be used as dietary fibers, thickening, gelling and stabilizing agents. Commercial alginates have vast applications in the fields of biomedical engineering, biotechnology, environmental contaminants treatments, food processing, and pharmaceuticals. Alginates can be used in wound dressings, bone regeneration, neovascularization, protein delivery, cell delivery, theranostic agents, oral drug delivery, controlled release systems, raft formulations, immobilization of biological agents and treatment of environmental contaminants. Various carrier systems can be formulated by the use of alginates like hydrogel, tablets, microcapsules, films, matrices, microspheres, liposomes, nanoparticles, beads, cochleate, floating and supersaturated drug delivery systems. This review presents a broad range of promising applications of alginates, and it can be a great interest to scientists and industries engaged in exploring its hidden potential.

Background: A combinational therapy is mostly preferred in hypertension treatment because of low-dose and less side effects like pretibial edema, and gastrointestinal bleeding. Objective: So the objective of the present work was to formulate an advanced drug delivery system in the form of bio-responsive microneedles by incorporating nifedipine, a cardiodepressant and diltiazem, a vasodilator for effective synergism in the treatment of hypertension. Methods: The pH-responsive PLGA nanospheres of diltiazem were formulated using Water-in-Oil-in- Water (W/O/W) double emulsion and solvent-diffusion-evaporation technique. These nanospheres were added to nifedipine-PVP mixture and then incorporated into mold to develop microneedles. Results: The microneedles showed the release of nifedipine almost 96.93± 2.31% for 24 h due to high PVP solubilization. The nanospheres of diltiazem on contact with acidic pH of skin managed to form of CO2 bubbles and increase the internal pressure to burst PLGA shell due to pore formation. The mean blood pressure observed for the normal group was 89.58 ± 3.603 mmHg, whereas the treatment with the new formulation significantly reduced the mean blood pressure up to 84.11 ± 2.98 mmHg in comparison to the disease control group (109.9 ± 1.825 mm Hg). Conclusion: This system co-delivers the drugs nifedipine and diltiazem in hypertension and shows an advance alternative approach over conventional drug delivery system.

Objective: Psoriasis is an inflamed skin disorder associated with the activation of phosphorylation signals in keratinocytes, which leads to proliferation. Phosphorylation signal inhibitors, such as silibinin can inhibit cell proliferation. Unlike current psoriasis treatment approaches that are associated with dangerous side effects; natural components can introduce new trends in psoriasis treatment. The major problem in the topical treatment of psoriasis is drug localization through the psoriasis lesions. Methods: In this study, silibinin-loaded polymeric micelles prepared and characterized for drug loading and release and ex vivo permeation through psoriatic and normal mice skin. The optimized batch was used for the treatment of psoriasis lesions in the mice model. Results: The optimized batch demonstrated mean particle size 18.3 ± 2.1 nm, entrapment efficiency 75.8 ± 5.8%, and prolonged silibinin release. % Silibinin permeated through psoriatic skin after 48 treated by polymeric micelle and aqueous control was 80.35, and 92.6, respectively. Polymeric micelles increased silibinin localization in the psoriatic skin in comparison with control. In psoriatic skin after 7- 10 days treatment by silibinin- loaded polymeric micelle, there was no evidence of psoriasis and the histological evaluation showed no sign of psoriasis. Silibinin-loaded polymeric micelles reduced Psoriasis area index by more than 78% after 14 days. Conclusion: It seems that polymeric micelles increased the effectiveness of silibinin by drug localization into the psoriatic plaque. Topical STAT- 3inhibitors can be introduced as a new strategy in psoriasis treatment.

Background: The encapsulation of anti-cancer drugs in stimulus-sensitive release systems may provide advantages such as enhanced drug toxicity in tumour tissue cells due to increased intracellular drug release. Encapsulation may also improve release in targeted tissue due to the response to a stimulus such as pH, which is lower in the tumour tissue microenvironment. Here, we evaluated the in vitro toxicity of the Drug Doxorubicin (DOX) loaded into a release system based on poly(β-amino ester)- modified MCM-41 silica nanoparticles. Methods: The MCM-41-DOX-PbAE release system was obtained by loading DOX into MCM-41 nanoparticles amino-functionalized with 3-aminopropyltriethoxysilane (APTES) and then coated with a pH-responsive poly(β-amino ester) (PbAE). The physicochemical characteristics of the release system were evaluated through TEM, FTIR and TGA. Cytotoxicity assays were performed on the MCM-41- DOX-PbAE system to determine their effects on the inhibition of human MCF-7 breast cancer cell proliferation after 48 h of exposure through crystal violet assay; the investigated systems included MCF-7 cells with MCM-41, PbAE, and MCM-41-PbAE alone. Additionally, the release of DOX and the change in pH in vitro were determined. Results: The physicochemical characteristics of the synthesized MCM-41-PbAE system were confirmed, including the nanoparticle size, spherical morphology, mesoporous ordered structure, and presence of PbAE on the surface of the MCM-41 nanoparticles. Likewise, we demonstrated that the release of DOX from the MCM-41-DOX-PbAE system promoted an important reduction in MCF-7 cell viability (~ 70%) compared to the values obtained with MCM-41, PbAE, and MCM-41-PbAE, as well as a reduction in the viability under treatment with just DOX (~ 50%). Conclusion: The results suggest that all the components of the release system are biocompatible and that the encapsulation of DOX in MCM-41-PbAE could allow better intracellular release, which would probably increase the availability and toxic effect of DOX.

Aim: This study aimed to investigate the existence of phospholipase-A (PLA) activity in Soluble L. major Antigens (SLA) because of no reports for it so far. Liposomes were used as sensors to evaluate PLA activity. Objectives: Liposomal SLA consisting of Egg Phosphatidylcholine (EPC) or Sphingomyelin (SM) were prepared by two different methods in different pH or temperatures and characterized by Dynamic Light Scattering (DLS) and Thin Layer Chromatography (TLC). Methods: Lipid hydrolysis led to the disruption of EPC liposomal SLA in both methods but the Film Method (FM) produced more stable liposomes than the Detergent Removal Method (DRM). Result: The preparation of EPC liposomal SLA at pH 6 via FM protected liposomes from hydrolysis to some extent for a short time. EPC liposomes but not SM liposomes were disrupted in the presence of SLA. Conclusion: Therefore, a phospholipid without ester bond such as SM should be utilized in liposome formulations containing PLA as an encapsulating protein.

Introduction: Atrophic vaginitis is a common problem in postmenopausal women and results from decreased levels of blood estrogen. It is associated with symptoms of itching, burning, dyspareunia, and postmenopausal bleeding. The present study evaluated the effects of fenugreek extract on atrophic vaginitis. Materials and Methods: This randomized controlled clinical trial was performed on 60 postmenopausal women in Ardabil, Iran, in 2018. The participants were selected using block randomization with the allocation ratio 1:1. Those in the intervention group received 0.5g (the applicator filled to the half-full mark) fenugreek vaginal cream 5% twice a week for 12 weeks. The control group received conjugated estrogens vaginal cream at the dose of 0.625 mg (the applicator filled to the half-full mark) containing 0.3 mg of conjugated estrogens. Atrophic vaginitis was evaluated before and after the treatment through clinical examination, clinical signs, and measurement of Vaginal Maturation Index (VMI). Findings: After the 12-week intervention and modification of the baseline score, the mean (standard error) score for atrophic vaginitis signs was 3.100 (1.43-4.75). This difference was statistically significant in intragroup comparison and in favor of the control group in intergroup comparison (p=0.001). VMI was less than 49% in 86.7% and 46.7% of the participants in the intervention and control groups, respectively. This was a significant difference in favor of the control group (p=0.001). Conclusion: The results of this study showed that total fenugreek extract could be effective in treating signs of atrophic vaginitis, but it was not as effective as ultra-low-dose estrogen.